ADDME - Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective

被引：71

作者：

Tsaioun, Katya ^{[1
]}

Bottlaender, Michel ^{[2
]}

Mabondzo, Aloise ^{[3
]}

机构：

[1] Apredica, Watertown, MA 02472 USA

[2] CEA, Serv Hosp Frederic Joliot, I2BM, F-91401 Orsay, France

[3] CEA, Serv Pharmacol & ImmunoAnalyse, IBiTec S, F-91191 Gif Sur Yvette, France

来源：

BMC NEUROLOGY | 2009年 / 9卷

关键词：

BLOOD-BRAIN-BARRIER; IN-VITRO; ENDOTHELIAL-CELLS; P-GLYCOPROTEIN; TOXICITY; PERMEABILITY; HEPATOTOXICITY; TRANSPORT; CULTURE; MODEL;

D O I：

10.1186/1471-2377-9-S1-S1

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The advent of early absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening has increased the attrition rate of weak drug candidates early in the drug-discovery process, and decreased the proportion of compounds failing in clinical trials for ADMET reasons. This paper reviews the history of ADMET screening and its place in pharmaceutical development, and central nervous system drug discovery in particular. Assays that have been developed in response to specific needs and improvements in technology that result in higher throughput and greater accuracy of prediction of human mechanisms of absorption and toxicity are discussed. The paper concludes with the authors' forecast of new models that will better predict human efficacy and toxicity.

引用

页数：11

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